Hormones friend or foe? Undertreatment and quality of life. No conflicts of interest to declare

Transcription

1 Hormones friend or foe? Undertreatment and quality of life Anette Tønnes Pedersen MD, Ph.D. Consultant, Associate professor Dept. Of Gynecology / Fertility Clinic Rigshospitalet No conflicts of interest to declare University of Copenhagen atp@dadlnet.dk

2 skin breast gastro-intestinal system bones brain cardio-vascular system ovaries uterus vagina

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4 The climacteric syndrome Irregular bleedings Vasomotor symptoms: Hot flushes and sweatings Joint and muscle ache Mood changes Anxiety Sleep disturbances Urogenital dysfunction: Atrophy, dryness Dyspareunia Incontinence Impairment of quality of life

5 The ovaries, after long years of service, have not the ability of retiring in graceful old age, but become irritated, transmit their irritation to the abdominal ganglia, which in turn transmit the irritation to the brain, producing disturbances in the cerebral tissue exhibiting themselves in extreme nervousness or in an outburst of actual insanity Farnham AM. Uterine disease as a factor in the production of insanity. 1887

6 1995: Consumption of HRT in women aged years calculated from sales statistics Denmark Norway Sweden Finland USA France Italy Spain Jolleys JV et al. Maturitas 1995

7 The New York Times July : Hormone Replacement Study A Shock to the Medical System B.T. 4. August 2002: Hormonbehandlinger øger risiko for sygdom Efter kvinder i årevis er blevet anbefalet hormonbehandling efter overgangsalderen, viser det sig nu, at bivirkningerne langt overstiger den ønskede virkning BMJ 4 October 2003: Head of German medicines body likens HRT to thalidomide

8 Design: Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women (JAMA 2002:288: ) Randomized, blinded, placebocontrolled primary prevention trial Study population: 16,608 postmenopausal women years with an intact uterus, recruited in Intervention: mg CEE mg MPA or placebo Follow-up: 5,2 years (planned 8,5 years)

9 Dagens Medicin, oktober 2003

10 Use of HT/HRT in Denmark Ref.: Lægemiddelstyrelsen 2006

11 Are we undertreating menopausal women? Post-WHI hormone fright

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14 HRT HT

15 HRT or HT.. HRT: Hormone Replacement Therapy HT: Hormone Treatment Indications: Premature Ovarian Insufficiency Climacteric symptoms Premature ovarian insufficiency: - amenorrhea, - elevated menopausal levels of gonadotropins - sex steroid deficiency in women less than 40 years old Ø prevent osteoporosis Ø prevent CVD Ø quality of life Ø symptom relief Ø urogenital dyscomfort Ø quality of life Adverse effects: Ø risk of endometrial hyperplasia and cancer Ø risk of breast cancer

16 18 years of estradiol measurements ØSTRADIOL 1,60 1,40 1,20 1,00 0,80 0,60 0,40 0,20 0,00 38,00 40,00 42,00 44,00 46,00 48,00 50,00 52,00 54,00 56,00 Normal estradiol Menopause

17 Hypothalamic regulation of hot flushes

18 Vasomotor symptom duration Median total VMS duration 7,4 years Avis NE, JAMA 2015

19 Vasomotor symptom duration Meta-Analysis Politi MC JGIM 2007

20 The effect of BMI on serum E2 and FSH levels during menopausal transition Population mean of E2: Population mean of FSH: Randolph Randolph JF JF et et al. al. J J Clin Clin Endocrinol Metab Metab

21 Higher BMI and current smoking behaviour are highly related to increased bother with vasomotor symptoms Ford K, Menopause 2005 A higher percentage of body fat is associated with increased odds of reporting vasomotor symptoms (per standard deviation increase in percent body fat: OR 1.27, 95% C.I ) SWAN study, Am J Epidemiol 2008 particularly subcutaneous adiposity, is associated with increased odds of hot flashes, favouring thermoregulatory models of hot flashes. SWAN study, Menopause 2008 Body fat gains are associated with greater hot flash reporting during menopausal transition. SWAN study, Am J Epidemiol 2009

22 Vasomotor symptom and bone turnover among early perimenopausal and late perimenopausal women, those with VMS had higher bone turnover than those without VMS. Prior to the final menstrual period, VMS may be a marker for risk of adverse bone health. Format: Abstract Crandall CJ, J Bone Miner Res. 2011

23 Sleep disturbance during the menopausal transition: Format: Abstract Kravitz HM, Sleep 2008

24 Subjective sleep disturbance and menopause: a meta-analysis Perimenopause vs. premenopause Surgical menopause vs. premenopause Format: Abstract Xu Q, Menopause 2014

25 NICE guidelines november 2015

26 NICE guidelines november 2015 Key conclusions : Strong evidence that transdermal estradiol plus progestogen greatly reduces the frequency of hot flushes in women with a uterus Although there was no strong evidence of efficacy of oral estrogen plus progestogen treatment, the health economic analysis and the Guideline Development Group s expert opinion supported its use in clinical practice. For the outcome of low mood, there is some evidence that HT may improve low mood for women in menopause.

27 Regimens? Dose? Administration? Monitoring? Duration?

28 HT og HRT - behandlingsregimer: Cyklisk gestagen Kontinuerlig østrogen Kontinuerlig østrogen, sekventiel gestagen Kontinuerlig østrogen, spaced out gestagen - long cycle Kontinuerlig kombineret østrogen og gestagen Østrogen og gestagen IUD Gestagen Østrogen

29 Postmenopausal HT - choice of regimen - Risk of breast cancer Estradiol + continuous progestogen Estradiol + cyclic progestogen Estradiol + long cycle progestogen Estradiol alone Risk of endometrial cancer

30 Peri- and postmenopausal HT Estradiol Continuously Transdermal preferred to oral therapy but what does the patient prefer? (compliance) Lowest dose for relief of symptoms Progestogen Only if there is a uterus! Does the patient already carry progestogen IUD? (Mirena) Cyclic preferred to continuous Duration Up to 5 years If there is a wish for continuation: information about potential risks Withdraw gradually over 6 month (?)

31 Peri- and postmenopausal HT Only urogenital complaints Local estradiol treatment - vagitorier, vaginal ring No systemic side-effects No limit in duration

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